Since their discovery, the function of MHC class II genes has been associated with immune regulations. Although conclusions drawn from structural studies on class II heterodimers have primarily confined their role to that of presentation of antigenic peptides along with the class I molecules, numerous studies have indicated that class II proteins and/or their processed peptides should not only be regarded as histocompatibility antigens, i.e. targets of immune reactions.
The development of numerous autoimmune diseases is associated with particular class II alleles although the specific implication of these class II alleles on either the presentation of self-antigenic peptides or the progression of autoimmune diseases has not yet been established. Conversely, the description of CD4 regulatory T cells (T-reg) associated with “resistance” to insulin-dependent diabetes mellitus (IDDM) or to other autoimmune pathologies has supported the involvement of class II/CD4 interactions in peripheral suppression of anti-self reactivity. The phenomenon of T cell-mediated suppression has, likewise, specific correlates to the MHC class II region. It has been shown that partial matching for class II loci between graft donor and recipient of vascularized organs had significant beneficial effects on survival of either kidney, heart or bone marrow (BM) transplants of large species including humans.
Broadening the spectrum of potential graft donors, by using donor/recipient pairs matched for class II loci would be highly desirable in clinical transplantation, but unfortunately cannot be achieved due to the extreme structural diversity of class II molecules.